Today the majority of human immune deficiency virus (HIV) infected patients in the US are on long-term (10+ years) antiretroviral therapy (ART). While ART suppresses HIV replication to below 50 copies / ml, not much is known about the long-term effect of these ART drugs on Kaposi sarcoma associated herpesvirus (KSHV) transmission and disease. We hypothesize that ART drug exposure contributes directly to a restriction in KSHV gene expression. If so, the mechanism could manifest itself in epigenetic modification of the viral episome and in altered release of micro RNAs in salivary exosomes. Such modification may respond differently to different drug regimens. Currently no other experimental studies investigate KSHV pathobiology in the background of multi-year exposure to ART drugs. This is a renewal application in response to PA-10- 290/Research on Malignancies in the Context of HIV/AIDS (R01).